Effects of isoflurane on acetylcholine receptor channels. 1. Single-channel currents

We studied the effects of the volatile general anesthetic isoflurane on single acetylcholine (ACh) receptor channels from clonal BC3H-1 cells. Excised patches were exposed to concentrations of isoflurane ranging from 0.18% to 4.0%, in the presence of 200 nM ACh. Isoflurane transformed channel behavior from isolated openings into bursts of brief openings. The channel open time decreased monotonically with the concentration of isoflurane; the mean open time was half of control at 0.4% isoflurane. The duration of bursts also decreased in the presence of isoflurane. The duration of brief closures within bursts was 300-400 musec at concentrations above 0.3% isoflurane. The number of openings per burst increased moderately with isoflurane but did not exceed 3. The frequency of bursts increased with the concentration of isoflurane. The apparent single-channel conductance decreased to 75% of control at 4% isoflurane. These results are discussed in terms of models of channel block. The concentration dependence of the open time, the gap duration, and the conductance are consistent with a sequential open-channel blocking mechanism in which most but not all blocking events were resolved. A model that assumes that isoflurane "blocks" both open and closed channels was then considered. This model is consistent not only with the open time data but also with the burst duration and number of openings per burst. These results indicate that isoflurane has effects on closed as well as open ACh receptor channels.